The Na ion pump, manifested in broken cell preparations as a Na ion, K ion -ATPase activity is important in the normal function of kidney, brain heart and many other tissues. The enzymic mechanisms of this pump involves an Na ion-dependent phosphorylation by ATP and a subsequent K ion-dependent dephosphorylation, but how this process produces transport of Na ion and K ion is not yet understood. Purified preparations of Na ion, K ion-ATPase contain at least two polypeptide subunits, but how these subunits are arranged to produce energy-linked vectorial ion movement is not known. Resolving the role of each subunit is hampered by the fact that dissociation of pump structure results in loss of Na ion, K ion-ATPase activity. The research proposed here is unique in that its objective is the isolation and purification of pump components without concern over this loss of ATPase activity. The key elements in this approach are two "partial" reactions catalyzed by the Na ion, K ion-ATPase: a Na ion-dependent ADP-ATP exchange and a K ion-dependent acetyl phosphatase activity. Our studies have shown that digitonin will disrupt membrane structure so that Na ion, K ion-ATPase activity is lost, but Na ion-dependent ADP-ATP exchange and K ion-dependent phosphatase activities survive. Subsequent results now indicate that ouabain binding is also somewhat affected and K ion-dependent p-nitrophenylphosphatase activity is strongly inhibited. Interaction of the surviving activities with Na ion and K ion occurs without change in cooperativity, but other kinetic constants of binding are altered. Preliminary results with a cross-linking agent suggest a change in subunit arrangement. A large decrease in enzyme particle size is also revealed by filtration data. Further enzymic characterization of the surviving activities is underway as a prelude to isolation of active fragments of the Na ion pump.